Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy.

Background: Clinical progression rate is the typical primary endpoint measure in progressive supranuclear palsy (PSP) clinical trials.

Objectives: This longitudinal multicohort study investigated whether baseline clinical severity and regional brain atrophy could predict clinical progression in PSP-Richardson's syndrome (PSP-RS).

Methods: PSP-RS patients (n = 309) from the placebo arms of clinical trials (NCT03068468, NCT01110720, NCT02985879, NCT01049399) and DescribePSP cohort were included.

Are reasons for first using cannabis associated with subsequent cannabis consumption (standard THC units) and psychopathology?

Background: Reasons for first using cannabis (RFUC) may influence later use patterns and mental health outcomes. However, limited research has explored self-medication versus social RFUCs in depth, and their associations with cannabis use patterns and psychopathology in the general population.

Objectives: We examined RFUCs and their associations with (1) reasons for continuing cannabis use, (2) weekly THC (delta-9-tetrahydrocannabinol) unit consumption and (3) symptoms of paranoia, anxiety and depressive symptoms.

Genetic analysis of GBA1 gene in a cohort of patients with Parkinson's disease.

Background: Variants in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are among the strongest genetic risk factors for Parkinson's disease (PD). While several pathogenic mutations are well-characterized, the impact of many rare or novel variants remains unclear.

Objective: This study is aimed to explore the spectrum of GBA1 variants in a cohort of PD patients from Southern Italy, with a particular focus on the clinical and structural characterization of a novel missense variant through integrated genetic and in silico analyses.

Distinct microRNA signatures define sporadic PSP-RS and PD in patient-derived midbrain organoids.

Progressive supranuclear Palsy-Richardson syndrome (PSP-RS) is a rare, rapidly progressive tauopathy often misdiagnosed as Parkinson's disease (PD) due to overlapping clinical features and the lack of reliable molecular biomarkers. To address this need, we generated human midbrain organoids from induced pluripotent stem cells (iPSCs) derived from individuals with sporadic PSP-RS, PD, and healthy controls (HCs), and performed longitudinal small RNA sequencing to profile microRNA (miRNA) signatures. These 3D organoids recapitulated disease-relevant pathologies, including tau hyperphosphorylation in PSP-RS and α-synuclein aggregation in PD.

Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes.

Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The gene encodes for tau protein. The locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased risk of PSP.

Bridging the Gap: Missing Data Imputation Methods and Their Effect on Dementia Classification Performance.

Missing data is a common challenge in neuroscience and neuroimaging studies, especially in the context of neurodegenerative disorders such as Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Inadequate handling of missing values can compromise the performance and interpretability of machine learning (ML) models. This study aimed to systematically compare the impacts of five imputation methods on classification performance using multimodal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Unveiling the neural network of freezing of gait in Parkinson's disease: A coordinate-based network study.

BackgroundFreezing of gait (FoG) is a debilitating symptom in Parkinson's disease (PD), yet its pathophysiological mechanisms remain poorly understood. Several studies have investigated the FoG neuroimaging correlates, with heterogeneous results.ObjectiveThis study investigated in a large PD cohort whether the disparate neuroimaging findings may converge to a common brain network.

Opicapone improves end-of-dose neuropsychiatric fluctuations in patients with Parkinson's disease.

Introduction: Non-motor fluctuations (NMF) represent one of the main complications that patients with Parkinson's disease (PD) may experience during long-term levodopa treatment. Opicapone (OPC), a COMT-inhibitor indicated for end-of-dose motor fluctuations (MF), has not been extensively investigated for the management of NMF. We evaluate the efficacy of OPC on end-of-dose neuropsychiatric fluctuations, the most frequent and severe NMF.

Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease driven by 4-repeat τ pathology, which is thought to propagate across interconnected neurons.

Objectives: We hypothesized that interconnected brain regions exhibit correlated atrophy, and that atrophy propagates network-like from fast-declining epicenters to connected regions in PSP.

Methods: We combined resting-state functional magnetic resonance imaging (fMRI) connectomics with two independent 12-month longitudinal structural magnetic resonance imaging (MRI) datasets of PSP-Richardson syndrome (PSP-RS) patients (n/n = 114/90).

Eye movement abnormalities in normal pressure hydrocephalus: a video-oculographic study.

Background: Eye movement dysfunction has been widely observed in several neurodegenerative diseases. Normal pressure hydrocephalus (NPH) is a treatable condition showing marked clinical and radiological overlap with neurodegenerative parkinsonism and dementia syndromes, often posing diagnostic challenges. The current study employed video-oculography (VOG) aiming to comprehensively explore possible ocular dysfunction in NPH patients.

Neuronally Derived Extracellular Vesicles' Oligomeric and p129-α-Synuclein Levels for Differentiation of Parkinson's Disease from Essential Tremor.

Clinical differentiation between Parkinson's disease (PD) and essential tremor (ET) may be challenging, highlighting the need for easily assessable diagnostic biomarkers. Neuronally derived extracellular vesicles (NDEVs) have been proposed as a peripheral matrix that can well recapitulate the cellular composition of neurons. We investigated the clinical usefulness of NDEV oligomeric and p129-α-synuclein levels in discriminating between patients with PD and those with ET.

Neuronally-Derived Extracellular Vesicles Transforming Growth Factor Beta-1 Levels in Progressive Supranuclear Palsy.

Background: Differentiating progressive supranuclear palsy (PSP) from other parkinsonian disorders may be challenging.

Objectives: To investigate the role of transforming growth factor beta-1 (TGFβ1) in PSP.

Methods: A total of 33 PSP, 39 Parkinson's disease (PD), 8 multiple system atrophy (MSA) patients, and 50 healthy controls (HC) were enrolled.

Eye movement abnormalities in Parkinson's disease motor subtypes: a video-oculographic study.

Introduction: Eye movement dysfunction has been described in Parkinson's disease (PD), but differences between tremor-dominant (TD) and postural instability/gait difficulty (PIGD) PD motor subtypes remain poorly understood. The aim of this study was thus to compare video-oculographic (VOG) features between PD motor subtypes.

Methods: Two hundred and four PD patients and 55 age-matched healthy control subjects (HC) were enrolled in this study.

Corrigendum: RT-ring: a small wearable device for tremulous Parkinson's disease diagnosis in primary care.

[This corrects the article DOI: 10.3389/fneur.2025.

Identification of Ser71Arg mutation in RAB32 gene in familial Parkinson's disease from Southern Italy.

We identified the RAB32 c.213 C > G variant in 7/300 unrelated familial PD patients (not found in 300 controls) from Southern Italy, screened by Sanger sequencing. We found a prevalence of 2.

Standardizing the large-volume "tap test" for evaluating idiopathic normal pressure hydrocephalus: a systematic review.

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait, cognitive, and urinary dysfunction associated with ventriculomegaly on neuroimaging. Clinical evaluation before and after CSF removal via large volume lumbar puncture (the "tap test") is used to determine a patient's potential to benefit from shunt placement. Although clinical guidelines for iNPH exist, a standardized protocol detailing the procedural methodology of the tap test is lacking.

First-Episode Psychosis incidence pre-, during, and post-COVID-19 pandemic: a six-year natural quasi-experimental study in South London.

Background: The COVID-19 pandemic may have been accompanied by an increased exposure to psychosis risk factors. We used a pre-during-post study design to examine variations in the incidence of First-Episode Psychosis (FEP) before, during, and after the COVID-19 pandemic in South London. We hypothesised that FEP rates rose during the pandemic and subsequently returned to pre-pandemic levels.

Volumetric Assessment and Graph Theoretical Analysis of Thalamic Nuclei in Essential Tremor.

Introduction: Essential tremor (ET) is a neurological disorder primarily characterized by upper limb action tremor. It is widely recognized that the thalamus is implicated in ET pathophysiology, playing a central role in treatment approaches. This study aimed to explore thalamic morphology, assessing macrostructural changes and intrinsic thalamic networks in ET patients.

RT-ring: a small wearable device for tremulous Parkinson's disease diagnosis in primary care.

Introduction: Differential diagnosis of rest tremor (RT) disorders is challenging, often requiring 123I-ioflupane single-photon-emission-computed tomography (DaTscan), an expensive technique not available worldwide. In the current study, we investigated the performance of a new wearable mobile device termed "RT-ring" in predicting DaTscan result in patients presenting with RT based on rest tremor inertial features.

Methods: Consecutive RT patients underwent RT-ring tremor analysis, surface electromyography (sEMG), and DaTscan.

Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).

Differential tractography identifies a distinct pattern of white matter alterations in essential tremor with or without resting tremor.

Essential Tremor (ET) is characterized by action tremor often associated with resting tremor (rET). Although previous studies have identified widespread brain white matter (WM) alterations in ET patients, differences between ET and rET have been less explored. In this study we employed differential tractography to investigate WM microstructural alterations in these tremor disorders.

Prospective Multicenter Evaluation of the MDS "Suggestive of PSP" Diagnostic Criteria.

Background: The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: "suggestive of PSP" for sensitive early diagnosis based on subtle clinical signs, "possible PSP" balancing sensitivity and specificity, and "probable PSP" highly specific for PSP pathology.

Objective: The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time.

Methods: Patients with "possible PSP" or "suggestive of PSP" diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP).

Serum Tau Species in Progressive Supranuclear Palsy: A Pilot Study.

Background/objectives: Progressive Supranuclear Palsy (PSP) is a tauopathy showing a marked symptoms overlap with Parkinson's Disease (PD). PSP pathology suggests that tau protein might represent a valuable biomarker to distinguish between the two diseases. Here, we investigated the presence and diagnostic value of six different tau species (total tau, 4R-tau isoform, tau aggregates, p-tau202, p-tau231 and p-tau396) in serum from 13 PSP and 13 PD patients and 12 healthy controls (HCs).

Generation of hiPSCs lines from three sporadic Parkinson's disease patients.

Here, we described the generation of human induced pluripotent stem cell lines (hiPSCs) from three sporadic Parkinson's disease (sPD) patients by reprogramming of their peripheral blood mononuclear cells (PBMC).

A proof-of-concept analysis of data from the first NHS clinic for young adults with comorbid cannabis use and psychotic disorders.

Background: Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.

Aims: Examine outcome data from the first 46 individuals to complete the CCP's intervention.